1. Field of the Invention
This invention relates to the field of alkylation processes and more particularly to alkylation processes wherein diazoalkane alkylation reagents are generated in situ.
2. Description of the Prior Art.
Many valuable organic syntheses involve alkylation reactions. These include, for example, the alkylation of alcohols and phenols to yield their corresponding ethers; the conversion of thioalcohols to thioethers; the alkylaton of carboxylic acids to yield their corresponding esters; and the alkylation of amines to yield alkylamines. Many other alkylation reactions are known, as well.
Alkylation reactions can be carried out using alkylation reagents, many of which are produced commercially. It appears, however, that usage of many well known alkylation reagents will be significantly restricted in the future, if not prohibited altogether, by imposition of governmental regulations such as those currently in existence or proposed by the Occupational Safety and Health Administration and/or Food and Drug Administration.
Additionally, there are some alkylation reagents which have not been used even without the new restrictions likely to be imposed. It has been known for many years, for instance, that diazoalkanes such as diazomethanes are exceptionally efficient alkylation reagents. Diazomethane is a yellow gas which has been used by the preparation of small quantities as an ethereal solution. The versatility of diazomethane in alkylations can be appreciated by noting that it can be reacted with carboxylic acids to form alkyl esters, or reacted with alcohols to form ethers, or reacted with acid chlorides to produce diazoketones, according to the Arndt-Eistert reaction, which can be decomposed to form carboxylic acids. The foregoing examples are only a few illustrations of the many possible alkylation reactions employing diazomethane, but they do serve to demonstrate its potential value as an alkylation reagent.
Despite this potential, diazomethane has been limited, by and large, to use in laboratory environments because of its many deleterious properties. It is, for example, highly toxic, potentially explosive, and is known tp cause development of specific sensitivity. Because of such properties, users are required to wear heavy gloves and safety goggles, and to work behind safety screens or hooded doors with safety glass. It is also recommended that ground points and sharp surfaces be avoided when using diazomethane as well as exposure to direct sunlight or strong artificial light which are believed to trigger diazomethane explosions. Particular care is also required with organic solvents having boiling points higher than ether so that explosive concentrations of diazomethane do not build up in the vapors above such solutions.